Jeremy Reiter
Jeremy Reiter is an Associate Professor at the Department of Biochemistry and Biophysics at the University of California, San Francisco. He received his B.A. in Molecular Biochemistry and Biophysics from Yale College, New Haven, Connecticut in 1993 and went on to do his Ph.D. in Genetics with Didier Y. R. Stainier at the University of California, San Francisco in 1999. After finishing his MD at UCSF, he completed a postdoctoral fellowship under the supervision of William C. Skarnes at the University of California Berkeley. He then moved back to UCSF and joined the Development and Stem Cell Biology Program in 2003. He obtained an Assistant professorship at the Department of Biochemistry and Biophysics in 2006 and became an associate professor in 2011. He has received numerous awards amongst them being the award as a National Academy of Science Kavli Fellow.
The Reiter Lab is interested in the role of cilia as critical mediators of intercellular signals during development. One crucial role is in the coordination of the Hedgehog signal transduction pathway. Hedgehog signals are essential regulators of embryonic patterning and cell proliferation, and defects in Hedgehog signaling are important causes of both birth defects and many cancers. The lab is particularly interested in understanding whether cilia transduce intercellular signals other than Hedgehog, how cilia interpret signals essential to vertebrate development and how cells regulate whether they form a cilium. Furthermore the lab is studying whether cilia participate in hedgehog-mediated oncogenesis. This work has begun to suggest that the primary cilium is an organelle dedicated to signal transduction, somewhat analogous to a cellular antenna. Ongoing work in the lab should reveal how this antenna interprets the signals required for normal development and homeostasis, and how malfunctions in the antenna contribute to cancer and other important human diseases.
A transition zone complex of ciliopathy proteins regulates ciliary composition
Primary cilia are projections found on many human cells. These cilia do not move, but function as cellular antennae to receive and interpret signals. For example, olfactory cilia sense signals from the environment, such as odorants. Other cilia sense cues from other cells, such as Hedgehog (Hh) proteins, to coordinate tissue patterning and growth. Defects in ciliary signaling cause some forms of birth defects, cancer, polycystic kidney disease, and other disorders collectively called ciliopathies. Investigating ciliopathies is illuminating how disturbing the function of a single organelle can give rise to diverse human diseases.
We have identified a complex of proteins that form part of the transition zone, a region at the base of the cilium. This complex includes the three members of the Tectonic family, extracytosolic glycoproteins that interact with transmembrane components of the transition zone such as Tmem67. These transmembrane proteins connect to a cytosolic transition zone complex comprised of most known Joubert- and Meckel-associated proteins.
Loss of components of this transition zone complex in mice compromise ciliogenesis in some tissues, and deregulate ciliary protein composition in others. In particular, the ciliary localization of Smoothened (Smo), a central component of the Hh pathway, depends on this complex. As Smo functions at the cilium, mouse transition zone mutants show deregulation of Hh signaling, resulting in ventralization of the neural tube and polydactyly.
Defining the components of the transition zone has led to the identification of genes underlying Joubert and Meckel syndromes. We hypothesize that these diseases are caused by transition zone dysfunction that disrupts intercellular signaling, leading to developmental defects.
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